This research has two major objectives. The first is to extend current knowledge of the deformability of normal and diseased erythroytes with particular emphasis on those properties which govern the individual cell's capacity to change shape in response to rapidly varying flow conditions. The second is to test the hypothesis that the additional shear stress imposed on the capillary endothelium by the passage of erythrocytes can modulate permeability and permeation and that reduced cellular deformability results in increased vascular permeation by plasma constituents. The methodology is predominantly experimental, consisting of (i) microrheologic studies of erythrocyte deformation in pure shear and pure extensional flows, (ii) physical/chemical characterizations of erythrocytes and erythrocyte membranes, and (iii) organ-perfusion studies designed to expose and quantify physiologic consequences of reduced deformability in the microvasculature of cardiac and skeletal muscle. Appropriate mathematical models will be applied to deduce intrinsic rheological properties of erythrocyte membrane from measurements of cellular elongation and extensional relaxation. Of particular interest is the question of reduced erythrocyte deformability in diabetes, sickle cell anemia, hereditary spherocytosis and various autoimmune hemolytic anemias. The information expected from this research is central to the long-term objective of elucidation of the structure and function of the microcirculation in health and disease.